Nurzigma (pridopidine) / Prilenia, Ferrer International - LARVOL DELTA

Prilenia and Ferrer Announce FDA Clearance to Start the “PREVAiLS” Pivotal Phase 3 Study with Pridopidine in ALS (Businesswire) - "Recruitment is planned to begin at the first US clinical trial sites in early 2026, with sites in Europe and other regions to follow, pending local clinical trial clearance...The study will consist of an initial 48-week double-blind placebo-controlled phase, randomized on a 3:2 (pridopidine:placebo) basis, followed by a 48-week open-label extension phase. The primary endpoint will be the change from baseline in ALSFRS-R adjusted for mortality at 48 weeks."

IND • New P3 trial • Amyotrophic Lateral Sclerosis

Huntington's disease clinical trials update: October 2025. (PubMed, J Huntingtons Dis) - "In this edition of the Huntington's Disease Clinical Trials Update, we expand on the launch of the phase II/III clinical trial of SKY-0515 from Skyhawk Therapeutics and the phase I/II clinical trial of SPK-10001 from Spark Therapeutics. Further updates include recent developments in Roche's tominersen programme within GENERATION HD2, progress with votoplam (PTC518) in PIVOT-HD by PTC Therapeutics and developments in the collaborative PTC Therapeutics/Novartis programme. We also report positive topline data from uniQure's phase I/II clinical trial of AMT-130 after 36 months of follow-up. We additionally discuss regulatory developments regarding pridopidine following the negative PROOF-HD study. Finally, we provide an updated listing of all registered and ongoing clinical trials in Huntington's disease."

Journal • Huntington's Disease • Movement Disorders

Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington’s Disease. (PubMed, Mol Neurobiol) - "The combination of these compounds may allow for lower efficacious doses leading to improved safety profiles and reduced off-target effects. This novel combinatorial approach, in which the S1R is activated while simultaneously inhibiting the S2R may prove to be a highly effective therapeutic strategy for HD and other neurodegenerative diseases."

Journal • CNS Disorders • Huntington's Disease • Retinal Disorders

Prilenia Therapeutics B.V. withdrew its application for the marketing authorisation of Nurzigma, a medicine intended for the treatment of adults with Huntington’s disease. (European Medicines Agency) - "The company withdrew the application on 7 November 2025."

European regulatory • Huntington's Disease

Pridopidine exerts neuroprotective effects through the activation of the sigma-1 receptor (S1R) by modulating ER stress in iPSC-derived neural progenitor cells (ALS-MND 2025) - "These findings highlight pridopidine's potential to enhance neuronal survival by mitigating ER stress, a key driver of ALS pathology. Given its ability to modulate fundamental disease mechanisms, pridopidine represents a promising therapeutic strategy for ALS."

CNS Disorders • Huntington's Disease • Movement Disorders • Psychiatry • BDNF • HSPA5

A planned phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pridopidine in participants with ALS (ALS-MND 2025) - "The HEALEY ALS Platform trial demonstrated a potential beneficial effect of pridopidine on ALS progression in a subgroup of rapidly progressing patients early in their disease course. A homogenous, rapidly progressive population is planned to be enrolled in order to determine a therapeutic effect within the limited timeframe of a clinical trial. Based on pridopidine's mechanism of action, it is anticipated that trial results will be extrapolatable to the broader population of people living with ALS."

Clinical • P3 data • CNS Disorders • Huntington's Disease • Movement Disorders

Prilenia and Ferrer plan to initiate a global confirmatory study of pridopidine in early-stage HD patients not taking ADMs - expected to commence in the first half of 2026. (Businesswire) - "In addition to the primary population, a small, proof-of-concept arm of patients taking low-dose ADMs (per label guidance) is also planned to be enrolled."

New trial • Huntington's Disease

pridopidine is in late-stage clinical development for ALS, with Prilenia and Ferrer planning to initiate a single, pivotal Phase 3 trial in ALS early in 2026, building on the findings in the population with early and rapid progressing disease (defined as definite or probable ALS by EEC and <18 months since symptom onset) from the Phase 2 HEALEY ALS Platform Trial. (Businesswire)

New P3 trial • Amyotrophic Lateral Sclerosis

Prilenia and Ferrer will present five posters at the 2025 HSG Huntington’s Disease (HD) Clinical Research Congress, including new analyses of 2-year data following patients not taking antidopaminergic medicines (ADMs) through both double-blind and open-label phases of PROOF-HD (Businesswire) - "...long term data showed a significant and clinically meaningful slowing of progression compared to propensity matched natural history cohorts from ENROLL-HD and TRACK-HD. Data at 2 years shows slowing of progression by 65% and 59% and (for TFC and cUHDRS respectively, both p = <0.0001), 88% for cognition (assessed by SWR, p = <0.0001) and 78% for motor features(assessed by Q-Motor, p = <0.0001) for pridopidine-treated patients off ADMs. Similar results were seen compared to Track-HD."

P3 data • Huntington's Disease

Efficacy and Safety of VMAT-2 Inhibitors and Dopamine Stabilizers for Huntington's Chorea: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis. (PubMed, Med Sci (Basel)) - "VMAT-2 inhibitors may suggest potential improvements in motor symptoms in Huntington's disease, while current evidence does not demonstrate a significant benefit of dopamine stabilizers. The safety profiles of both treatments appear generally comparable to placebo. Further rigorous and long-term studies are required to better establish their efficacy and safety."

Clinical • Journal • Retrospective data • Review • Genetic Disorders • Huntington's Disease • Movement Disorders

The OLE portion of the PROOF-HD trial shows persistent benefits of pridopidine on function, cognition, and motor in HD (EAN 2025) - "Pridopidine shows consistent, sustained and clinically meaningful benefits across multiple endpoints of HD progression through 2 years."

CNS Disorders • Huntington's Disease • Movement Disorders

Nature Medicine Publishes Phase 3 Data on Pridopidine in Early-Stage Huntington’s Disease, Highlighting Impact on Clinical Progression (Businesswire) - "The published data, from pre-defined analyses of a subgroup of patients not taking ADMs from pridopidine’s Phase 3 PROOF-HD trial, show that treatment with pridopidine achieved a clinically meaningful improvement from baseline for one year and slowing of decline thereafter, as measured by cUHDRS, with change vs placebo of ­0.46, ­0.45, ­0.41 and ­0.27 at 26, 39, 52 and 65 weeks (the end of the double-blind trial)."

P3 data • Huntington's Disease

Pridopidine in early-stage manifest Huntington's disease: a phase 3 trial. (PubMed, Nat Med) - P3 | "Taken together, pridopidine has the potential to address a critical unmet need in HD. ClinicalTrials.gov identifier: NCT04556656 ."

Clinical • Journal • P3 data • CNS Disorders • Huntington's Disease • Movement Disorders

Prilenia and Ferrer Provide Update on European Regulatory Process for Pridopidine in Huntington’s Disease (Businesswire) - "Prilenia Therapeutics B.V. and Ferrer today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the refusal of the marketing authorization for pridopidine’s marketing authorization application for Huntington’s disease (HD)...We are disappointed, but undeterred in our commitment to bring what we believe is an effective therapy to patients and will explore all options collaboratively with regulators....Near-term plans are in place to initiate a potentially registrational global HD study, to provide confirmation of the previously observed pridopidine results, and a pivotal global Phase 3 ALS study, with recruitment for both expected to start as soon as possible."

CHMP • New P3 trial • Amyotrophic Lateral Sclerosis • Huntington's Disease

Prilenia Enters into a Collaboration and License Agreement with Ferrer for the Commercialization and Co-Development of Pridopidine in Europe and Other Select Markets (Businesswire) - "Prilenia Therapeutics...today announced that it has entered into a collaboration and license agreement with Ferrer for the commercialization and further development of pridopidine in Europe and other select markets. Pridopidine is a potent and highly selective, orally administered sigma-1 receptor (S1R) agonist designed to regulate key neuroprotective mechanisms often impaired in neurodegenerative diseases such as HD and ALS. Under the terms of the agreement, Prilenia will receive an upfront payment of approximately €80 million plus up to €45 million in near-term development, regulatory, and commercial milestones....Our MAA has been accepted for review, and we expect an opinion from the Commission for Medicinal Human Products (CHMP) in the second half of 2025....For ALS, Prilenia and Ferrer plan to initiate a single, pivotal Phase 3 trial to evaluate pridopidine..."

CHMP • Licensing / partnership • New P3 trial • Amyotrophic Lateral Sclerosis • Huntington's Disease

PRidopidine's Outcome On Function in Huntington Disease, PROOF- HD (clinicaltrials.gov) - P3 | N=499 | Completed | Sponsor: Prilenia | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Huntington's Disease • Movement Disorders

Pridopidine in Amyotrophic Lateral Sclerosis: The HEALEY ALS Platform Trial. (PubMed, JAMA) - P2/3 | "In this 24-week study, pridopidine did not impact the progression of ALS. ClinicalTrials.gov Identifiers: NCT04297683, NCT04615923."

Clinical • Journal • Amyotrophic Lateral Sclerosis • CNS Disorders

The Safety Profile of Pridopidine, a Novel Sigma-1 Receptor Agonist for the Treatment of Huntington's Disease. (PubMed, CNS Drugs) - "The integrated analysis replicated and corroborated the good safety profile observed in the individual studies. Despite the larger sample size, no new safety signals emerged. Long-term exposure to pridopidine, up to 6.5 years in open-label extension studies, revealed no new safety concerns, supporting its potential for long-term use in patients with HD."

Journal • CNS Disorders • Huntington's Disease • Movement Disorders

Pridopidine for the Treatment of ALS–Improvements in the Subgroup of Definite, Probable, and Early (<18mo from Onset) Subjects in the Phase 2 Healey ALS Platform Trial (AAN 2025) - "Pridopidine demonstrated beneficial effects across multiple clinical measures of ALS, including survival benefits in definite+probable ALS and early participants. These encouraging observations support and inform planning for a Ph3 study."

Clinical • P2 data • Pulmonary Disease • HSPA5

The Phase 3 PROOF-HD Trial Demonstrates Meaningful Benefits of Pridopidine on Function, Cognition, and Motor Signs in Huntington Disease (HD) (AAN 2025) - "Pridopidine shows consistent, sustained, and clinically meaningful benefits across multiple endpoints including function, clinical progression, cognition, motor and QoL in subjects off and on low doses of ADMs."

P3 data • Genetic Disorders • Huntington's Disease • Movement Disorders

A narrative review of phase III and IV clinical trials for the pharmacological treatment of Huntington's disease in adults. (PubMed, Medicine (Baltimore)) - "The medications used in phase III and IV trials are minocycline, valbenazine, deutetrabenazine, tominersen, pridopidine (phase III), and memantine (phase IV)...Current medications aim to manage HD symptoms, potentially improving outcomes and reducing disease progression risks. The growing emphasis on specific approaches reflects a better understanding of HD's diverse symptoms, presenting opportunities for more effective and personalized treatment strategies."

Journal • P3 data • Review • CNS Disorders • Genetic Disorders • Huntington's Disease • Movement Disorders • Psychiatry

Targeting the sigma-1 receptor with pridopidine induces functional neurorestoration in spinal cord ischemia-reperfusion injury. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Prdpn improved spinal cord IRI-induced behavioral deficits through its antioxidant, anti-inflammatory, anti-apoptotic, and neurotrophic properties. It suggests promise as a potential treatment option to stop spinal cord IRI."

Journal • Cardiovascular • Reperfusion Injury • BDNF • CASP3 • IL1B • TNFA

Pridopidine for the treatment of ALS – significant improvements in definite, probable, and early (<18 mo from onset) subjects in the Phase 2 Healey ALS platform trial (ALS-MND 2024) - "In summary, pridopidine demonstrated beneficial effects across multiple clinical measures of ALS, as well as survival benefits in definite ± probable ALS and early participants. These encouraging observations support and inform planning for a Ph3 study."

Clinical • P2 data • Pulmonary Disease

Prilenia to Present Pridopidine Data at the Huntington Study Group (HSG) 2024 Congress (Businesswire) - "Prilenia Therapeutics B.V...today announced the presentation of five scientific abstracts and an oral presentation focused on pridopidine, the company’s investigational medicine for the treatment of Huntington’s disease (HD), at the upcoming 31st annual meeting of the Huntington Study Group to be held in Cincinnati, Ohio, November 7-9, 2024."

P3 data • CNS Disorders • Huntington's Disease

The Phase 3 PROOF-HD Trial Demonstrates Significant Benefits of Pridopidine on Progression, Cognition, and Motor Function in Huntington Disease (HD) (HSG 2024) - "Pridopidine shows consistent, sustained, and clinically meaningful benefits across multiple endpoints including function, disease progression, cognition, motor and QoL in subjects off and on low doses of ADMs."

P3 data • Behavior Disorders • Genetic Disorders • Huntington's Disease • Mental Retardation • Movement Disorders • Psychiatry